This invention generally relates to a medicated prosthesis or implant. More particularly, the invention relates to a medicated intra-vascular prosthesis, such as a stent, that is radially expandable in the vasculature of a patient and delivers a therapeutic agent to the site of implantation.
Stents are generally cylindrically shaped prosthetic implants which function to hold open and sometimes expand a segment of a blood vessel or other anatomical lumen. They are particularly suitable for supporting and preventing a torn or injured arterial lining from occluding a fluid passageway. Intravascular stents are very useful for treatment of coronary artery stenoses, and for reducing the likelihood of the development of restenosis or closure after balloon angioplasty.
The success of a stent can be assessed by evaluating a number of factors, such as the degree of development of thrombosis; degree of neointimal hyperplasia or smooth muscle cell migration and proliferation following implantation of the stent; severity of injury to the artery wall; overall loss of luminal patency; stent diameter in vivo; thickness of the stent; and leukocyte adhesion to the luminal lining of stented arteries. However, the chief areas of concern are early subacute thrombosis, and eventual restenosis of the blood vessel due to intimal hyperplasia.
Therapeutic pharmacological agents have been developed to improve successful placement of the stent and are delivered to the site of stent implantation. Stents that are of a common metallic structure were previously unable to deliver localized therapeutic pharmacological agents to a blood vessel at the location being treated with the stent. There are polymeric materials that can be loaded with and release therapeutic agents. However, these polymeric materials may not fulfill the structural and mechanical requirements of a stent, especially when the polymeric materials are loaded with a drug, since drug loading of a polymeric material can significantly reduce the structural and mechanical properties of the polymeric material.
It has been known in the art to coat a metallic stent with a polymeric material and load the polymeric material with a drug. Altematively, stents of polymeric materials have been reinforced with metal structure. These stent designs have the strength necessary to hold open the lumen of the vessel because of the reinforced strength of the metal. Stents made of both polymeric material and metal have a larger radial profile because the volume occupied by the metal portion of the stent cannot absorb and retain drugs. Reducing the profile of a stent is preferable because it increases the in vivo diameter of the lumen created by the stent. Thus it is desirable to configure a metallic stent to deliver drugs to the blood vessel walls without substantially increasing the profile of the stent. The present invention meets these needs.
In accordance with one embodiment, a stent is provided comprising a body wherein at least a part of the body includes a first porous region and a second porous region disposed beneath the first porous region, the second porous region containing a therapeutic substance for the local delivery of the substance when the stent has been implanted in a vessel, wherein the average pore size of the first porous region is less than the average pore size of the second porous region for reducing the rate of release of the therapeutic substance from the second porous region. A film layer, for example a polymeric layer, can be additionally disposed over the first porous region. The therapeutic substance can be for the treatment of restenosis. In one embodiment, the stent includes a third porous region, wherein the second porous region is disposed between the first and third porous regions and wherein the average pore size of the third porous region is less than the average pore size of the second porous region.
In accordance with another embodiment, a stent comprising a strut element is provided, wherein the strut element includes a inner core made from a first porous metallic material and an outer core surrounding the inner core made from a second porous metallic material. The average pore size of the second material can be less than the average pore size of the first material. The inner core can include a therapeutic substance for release of the substance when the stent has been implanted in a vessel. The outer core reduces the rate of release of the substance from the inner core.
In accordance with another embodiment, a stent is provided comprising a body wherein at least a part of the body is made from sintering elongated metallic fibers together to make a porous structure.
In accordance with yet another embodiment, a method of manufacturing a stent is provided, comprising sintering particles of a first size together to form a first porous network, and sintering particles of a second size together and to the first porous network to form a second porous network, wherein the first size is greater than the second size so that the first porous network has an average pore size that is greater than the average pore size of the second porous network. The method can additionally include depositing a therapeutic substance in the first porous network for the local delivery of the substance after the stent has been implanted in the body of a patient, wherein the second porous network reduces the rate of release of the substance from the stent. A polymeric film layer can be deposited on the second porous network. In one embodiment, the particles of the second size are sintered all the way around the first porous network such that the second porous network completely surrounds the first porous network.
In accordance with yet another embodiment, a method of manufacturing a stent is provided, comprising sintering elongated fibers together to form a component of the stent body.